RecruitingPhase 2NCT07486817

Beamion 44: A Study to Test How Well Zongertinib is Tolerated by People With Advanced Non-small Cell Lung Cancer With HER2 Mutations When Given in Combination With Chemotherapy With or Without Pembrolizumab

Beamion 44: A Randomized, Open-label, Multi-center Phase IIa Platform Trial to Evaluate the Safety and Tolerability of Zongertinib Plus Platinum-based Doublet Chemotherapy With or Without Pembrolizumab (and Potential Other Combinations) in Treatment-naïve Patients With Locally Advanced/Metastatic Non-squamous NSCLC With Activating HER2 Mutations


Sponsor

Boehringer Ingelheim

Enrollment

60 participants

Start Date

Jun 4, 2026

Study Type

INTERVENTIONAL

Conditions

Summary

This study is open to adults with a type of lung cancer called HER2-mutant non-squamous non-small cell lung cancer (NSCLC) that is advanced or has spread. People who have a tumor with a HER2 mutation and have not received previous treatment for their lung cancer can participate in the study. The purpose of this study is to find out how well a medicine called zongertinib is tolerated in people with this type of lung cancer, when combined with chemotherapy, with or without pembrolizumab. Zongertinib works by targeting and blocking HER2, a protein involved in cancer cell growth. Participants are put into two groups randomly, which means by chance. One group gets zongertinib tablets combined with platinum-based chemotherapy. The other group gets the same treatment plus an additional medicine called pembrolizumab. Chemotherapy and pembrolizumab are given as an infusion into a vein. Participants take zongertinib by mouth once a day, while chemotherapy is given every 3 weeks for up to 3 months, followed by maintenance treatment for up to 2 years. Pembrolizumab is given every 3 weeks for up to 2 years. This study does not have a fixed duration. Participants can receive some of the study treatments for up to about 2 years and may continue to take zongertinib as long as they benefit from treatment and can tolerate it. During this time, they visit the study site regularly. Doctors regularly check the size of the tumor and whether it has spread. They also monitor participants' health and take note of any unwanted effects.


Eligibility

Min Age: 18 Years

Inclusion Criteria7

  • Patients ≥18 years of age or over the legal age of consent in countries where that is greater than 18 years at the time of signature of the informed consent form (ICF)
  • Histologically or cytologically confirmed diagnosis of an advanced and/or metastatic non-squamous non-small cell lung cancer (NSCLC)
  • Documented activating human epidermal growth factor receptor 2 (HER2) mutation as per existing local lab result
  • An archival tumor tissue sample must be submitted to the central laboratory after randomization to retrospectively confirm the HER2 status
  • Patients who have not received any systemic treatment for unresectable, locally advanced or metastatic disease
  • Presence of at least one measurable non-Central Nervous System (CNS) lesion according to response evaluation criteria in solid tumors (RECIST) 1.1
  • Eligible to receive treatment with the selected platinum based doublet chemotherapy and pembrolizumab in accordance with the summary of product characteristics (SmPC)/Product Information

Exclusion Criteria6

  • Tumors with targetable alterations with approved available therapy
  • Presence or history of leptomeningeal disease
  • Radiotherapy within 4 weeks prior to treatment start with exception of palliative radiotherapy to regions other than the chest if completed at least 2 weeks prior to treatment start
  • Major surgery (major according to the investigator's assessment) performed within 4 weeks prior to randomization or planned within 6 months after screening
  • Any history of or concomitant condition that, in the opinion of the investigator, would compromise the patient's ability to comply with the trial or interfere with the evaluation of the safety and efficacy of the test drug
  • Previous therapy with a HER2-directed agent

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Interventions

DRUGZongertinib

Zongertinib

DRUGCisplatin

Cisplatin

DRUGCarboplatin

Carboplatin

DRUGPemetrexed

Pemetrexed

DRUGPembrolizumab

Pembrolizumab


Locations(17)

Royal North Shore Hospital

St Leonards, New South Wales, Australia

Cabrini Health

Malvern, Victoria, Australia

Fiona Stanley Hospital

Murdoch, Western Australia, Australia

Guangdong Provincial People's Hospital

Guangzhou, China

Shanghai Geriatric Medical Center

Shanghai, China

CTR Leon Berard

Lyon, France

INS Curie

Paris, France

Universitätsklinikum Köln (AöR)

Cologne, Germany

Thoraxklinik-Heidelberg gGmbH am Universitätsklinikum Heidelberg

Heidelberg, Germany

Kindai University Hospital

Osaka, Sakai, Japan

National Cancer Center Hospital

Tokyo, Chuo-ku, Japan

Severance Hospital

Seoul, South Korea

Asan Medical Center

Seoul, South Korea

Samsung Medical Center

Seoul, South Korea

Hospital Universitari Vall d'Hebron

Barcelona, Spain

Hospital Universitario 12 de Octubre

Madrid, Spain

Hospital Virgen del Rocío

Seville, Spain

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NCT07486817


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